Herpes Zoster: Comprehensive Overview
Definition and Pathophysiology
Herpes zoster (shingles) is caused by reactivation of latent varicella zoster virus (VZV) in dorsal root and cranial nerve ganglia, occurring when VZV-specific cell-mediated immunity declines due to aging or immunosuppression. 1
- After primary varicella infection (chickenpox), VZV establishes latency in neuronal ganglia and can reactivate years or decades later 1
- The reactivation is directly linked to declining cell-mediated immunity, which occurs naturally with aging, particularly after age 50 1
- Approximately 20-30% of people develop herpes zoster over their lifetime, with incidence increasing markedly beginning at age 50 1
- The lifetime risk may reach 50% among those aged ≥85 years 1
Epidemiology
The overall incidence of herpes zoster ranges from 1.2 to 4.8 cases per 1000 person-years in Western populations, with significantly higher rates in immunocompromised individuals. 1
- In Taiwan, the overall incidence is 4.97 cases per 1000 person-years, with higher rates in women (5.20 vs 4.72 per 1000 person-years in men) 1
- The estimated lifetime risk of occurrence is 32.2% in the general population 1
- Immunocompromised adults have dramatically elevated risk, with incidence rates ranging from 9 to 95 cases per 1000 person-years 1
- The highest incidence occurs in hematopoietic stem cell transplant recipients, followed by hematologic malignancies, solid organ transplantation, and solid cancers 1
Risk Factors for Increased Incidence
- Age ≥50 years (most significant risk factor) 1, 2
- Immunocompromised status including HIV/AIDS (RR 1.53), hematologic malignancies, and transplant recipients 1
- Autoimmune diseases: systemic lupus erythematosus (RR 2.12), rheumatoid arthritis (RR 1.51) 1
- Diabetes mellitus (RR 1.52) 1
- Malignancies: breast cancer (RR 1.57), liver cancer (RR 1.19) 1
- COVID-19 infection (adjusted IRR 1.15 in patients aged ≥50 years) 1
Clinical Manifestations
Herpes zoster typically presents as a painful, unilateral vesicular rash in a dermatomal distribution, often preceded by prodromal symptoms of pain, fever, and itching. 2, 3
Prodromal Phase
- Fever, pain, and pruritus commonly occur before rash onset 3
- Pain may precede the rash by several days 2
Acute Phase
- Characteristic unilateral vesicular eruption following a dermatomal distribution 2, 4
- Lesions progress from macules to papules, vesicles, pustules, and finally crusts 1
- The rash typically lasts approximately 4 weeks in untreated patients 5
- Most commonly affects the trunk, but can occur anywhere including the head and neck 4
Special Presentations
- Herpes zoster ophthalmicus (involvement of the ophthalmic division of the trigeminal nerve) requires urgent treatment 4
- Disseminated herpes zoster can occur in immunocompromised patients 4
- Atypical presentations are more common in immunocompromised individuals 6
Complications
Postherpetic neuralgia (PHN), defined as pain persisting more than 3 months after rash healing, is the most common and debilitating complication, particularly in elderly patients. 2, 3
Postherpetic Neuralgia
- Occurs in approximately 4% of herpes zoster cases aged >75 years 1
- Risk increases significantly with age 2, 5
- Can persist for months to years and severely impacts quality of life 2, 5
- Associated with higher healthcare utilization including outpatient visits, emergency room visits, and hospitalizations 1
Other Complications
- Ophthalmic complications (zoster ophthalmicus) 4
- Peripheral and central nervous system involvement 4
- Secondary bacterial infection of skin lesions 6
- Increased mortality in immunocompromised individuals 6
Recurrence Risk
- A second episode of herpes zoster is uncommon in immunocompetent hosts but occurs more frequently in immunocompromised patients 1
- The 10-year cumulative recurrence risk is 10.3% 7
Diagnosis
The diagnosis of herpes zoster is primarily clinical, based on the characteristic appearance and dermatomal distribution of the rash. 2, 4
Clinical Diagnosis
- Unilateral vesicular rash in dermatomal distribution is pathognomonic 2, 4
- History of prodromal pain and characteristic progression of lesions supports diagnosis 2
Laboratory Testing
- PCR is the gold standard for laboratory confirmation when needed 4
- Direct identification of VZV in cell cultures 4
- Detection of IgM and IgA anti-VZV antibodies may be helpful in immunocompromised patients 4
- Laboratory testing is required for atypical presentations or suspected CNS involvement 6
Treatment
Systemic antiviral therapy should be initiated within 72 hours of rash onset to reduce severity, duration of acute phase, and risk of complications, particularly PHN. 6, 4, 5
Antiviral Therapy
Valacyclovir or famciclovir are the preferred first-line agents due to superior pharmacokinetics and more convenient dosing compared to acyclovir. 6, 5
First-Line Options
- Valacyclovir: Produces plasma levels equivalent to intravenous acyclovir, dosed 3 times daily for 7 days, and has been shown to be more effective than acyclovir in shortening PHN duration 5
- Famciclovir: Dosed 3 times daily for 7 days, equally effective as valacyclovir 6, 5
Alternative Options
- Acyclovir: Dosed 5 times daily for 7 days, less convenient but effective 4, 5
- Brivudin (available in some countries): Once-daily dosing for 7 days, markedly higher anti-VZV potency than oral acyclovir, no nephrotoxic properties 4
Urgent Indications for Antiviral Therapy
- All patients aged >50 years 4
- Herpes zoster in the head and neck area, especially zoster ophthalmicus 4
- Severe herpes zoster on trunk or extremities 4
- Immunosuppressed patients at any age 4
- Patients with severe atopic dermatitis or eczema 4
Relative Indications
- Patients <50 years with zoster on trunk or extremities have only relative indications for antiviral therapy 4
Pain Management
Appropriately dosed analgesics combined with neuroactive agents (such as amitriptyline) should be initiated early alongside antiviral therapy to achieve painlessness. 4
- Analgesics for acute zoster pain control 6
- Neuroactive agents (amitriptyline) in combination with analgesics 4
- For established PHN: topical lidocaine patches, gabapentin, or pregabalin 6
Corticosteroid Therapy
- May shorten the degree and duration of acute zoster pain when added to antiviral therapy 4
- Does not have essential effect on development of PHN 4
- One study showed corticosteroids plus acyclovir improved quality of life in older patients, while another showed no added benefit 5
Supportive Care
Early Pain Specialist Referral
- Recommended in specific cases where PHN develops, as it is very difficult to treat 4
Prevention
All adults aged ≥50 years should receive the recombinant zoster vaccine (Shingrix/RZV) as a 2-dose series, regardless of prior herpes zoster history or previous Zostavax vaccination. 7
Recombinant Zoster Vaccine (Shingrix/RZV)
Efficacy
- 97.2% efficacy in preventing herpes zoster in adults aged ≥50 years 7
- Protection persists for at least 8 years with minimal waning, maintaining efficacy above 83.3% 7
- Significantly superior to the older live-attenuated Zostavax vaccine 7
Dosing Schedule
- Standard schedule: Second dose given 2-6 months after first dose 7
- Immunocompromised adults: Shorter schedule with second dose 1-2 months after first dose 7
- Minimum interval between doses is 4 weeks 7
- Administered intramuscularly 7
Recommended Populations
- All adults aged ≥50 years 7
- Immunocompromised adults aged ≥18 years (including those on immunosuppressive therapy, with autoimmune diseases, transplant recipients, cancer patients) 7
- Adults with prior herpes zoster history (wait at least 2 months after acute episode resolves) 7
- Adults who previously received Zostavax (wait at least 2 months after Zostavax) 7
Advantages Over Zostavax
- Non-live recombinant vaccine, safe for immunocompromised patients 7
- Maintains high efficacy across all age groups (Zostavax efficacy: 70% in ages 50-59 vs. 18% in ≥80 years) 7
- Zostavax efficacy wanes to only 14.1% by year 10 7
Side Effects
- Injection-site reactions (pain, redness, swelling) common: 9.5% grade 3 reactions vs. 0.4% with placebo 7
- Systemic symptoms: 11.4% vs. 2.4% in placebo 7
- No serious safety concerns identified in large clinical trials 7
Special Considerations
- Can be administered to patients on low-dose glucocorticoids (<10 mg/day prednisone equivalent) without adversely impacting vaccine response 7
- For patients with autoimmune inflammatory rheumatic diseases, Shingrix is strongly preferred over live-attenuated vaccine 7
- No minimum interval required when transitioning from Zostavax to Shingrix 7
Infection Control Measures
- Routine hand hygiene 6
- Appropriate isolation precautions and personal protective equipment 6
- Varicella-zoster immunoglobulin for post-exposure prophylaxis in susceptible individuals 6
Key Clinical Pitfalls to Avoid
- Do not delay antiviral therapy beyond 72 hours of rash onset - efficacy decreases significantly after this window 6, 4
- Do not use live-attenuated Zostavax in immunocompromised patients - only Shingrix is appropriate for this population 7
- Do not assume prior herpes zoster provides adequate protection - vaccination is still recommended due to 10.3% recurrence risk at 10 years 7
- Do not overlook zoster ophthalmicus - this requires urgent antiviral therapy to prevent vision-threatening complications 4
- Do not rely solely on antivirals for pain management - early combination with analgesics and neuroactive agents is essential 4
Common Viva Questions and Answers
Q: What is the pathophysiology of herpes zoster? A: Reactivation of latent VZV in dorsal root ganglia due to declining cell-mediated immunity, most commonly with aging or immunosuppression 1
Q: What is the most common complication of herpes zoster? A: Postherpetic neuralgia (PHN), defined as pain persisting >3 months after rash healing, occurring in approximately 4% of cases aged >75 years 1, 2
Q: What is the therapeutic window for antiviral therapy? A: Within 72 hours of rash onset for maximum efficacy in reducing severity and complications 6, 4
Q: Which patients require urgent antiviral therapy? A: All patients >50 years, head/neck involvement (especially zoster ophthalmicus), immunosuppressed patients, and severe disease 4
Q: What is the preferred antiviral agent? A: Valacyclovir or famciclovir due to superior pharmacokinetics and convenient dosing (3 times daily vs. 5 times daily for acyclovir) 6, 5
Q: What is the recommended vaccine for herpes zoster prevention? A: Shingrix (recombinant zoster vaccine) as a 2-dose series for adults ≥50 years, with 97.2% efficacy 7
Q: Can immunocompromised patients receive the herpes zoster vaccine? A: Yes, but only Shingrix (RZV), not the live-attenuated Zostavax, which is contraindicated in immunocompromised individuals 7
Q: What is the recurrence risk after one episode of herpes zoster? A: 10.3% cumulative recurrence risk at 10 years, which is why vaccination is recommended even after a prior episode 7